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Ronaldo started in United’s previous four games but is absent from the 20-man squad for the visit of Villa at Old Trafford.
United have one more game in the Premier League at Fulham on Sunday before the domestic season is halted to accommodate the World Cup.
Ronaldo, who appeared in the 2006, 2010, 2014 and 2018 finals, was named in the Portugal squad that was announced on Thursday evening.
Fellow United forwards Antony and Jadon Sancho are again absent. Antony has been unavailable for the last two weeks with a leg injury and Jadon Sancho has been missing for a similar period due to illness.
Ten Hag said to MUTV: “Jadon ill, Cristiano ill and Antony injured.”
Ronaldo has only scored three times for United this season when he had three times as many club goals this time last year.
The 37-year-old scored against FC Sheriff home and away in the Europa League and he also struck the winner at Everton last month.
Anthony Martial will make only his third United start in the last year.